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-Structure paper
タイトル | Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1. |
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ジャーナル・号・ページ | Acta Pharmacol Sin, Vol. 44, Issue 6, Page 1227-1237, Year 2023 |
掲載日 | 2022年12月8日 |
![]() | Li-Hua Zhao / Qing-Ning Yuan / An-Tao Dai / Xin-Heng He / Chuan-Wei Chen / Chao Zhang / You-Wei Xu / Yan Zhou / Ming-Wei Wang / De-Hua Yang / H Eric Xu / ![]() ![]() |
PubMed 要旨 | Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and ...Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor-1 (PTH1R), a member of class B G protein- coupled receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.62 Å and 3.25 Å, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders. |
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手法 | EM (単粒子) |
解像度 | 2.62 - 3.76 Å |
構造データ | EMDB-34585, PDB-8ha0: EMDB-34587, PDB-8haf: EMDB-34598, PDB-8hao: |
化合物 | ![]() ChemComp-CLR: ![]() ChemComp-PLM: |
由来 |
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![]() | LIPID BINDING PROTEIN/HORMONE/IMMUNE SYSTEM / PTH1R / GPCR / LIPID BINDING PROTEIN-HORMONE-IMMUNE SYSTEM complex |